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Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as “the composite of all the physical and mental capacities that an individual can draw on at any point in time”. Vitality capacity is considered the underlying physiological determinant of intrinsic capacity. To advance the measurement and monitoring of vitality capacity, a working group of WHO staff members and twenty experts representing six WHO regions was convened to discuss and clarify the attributes of vitality capacity and to develop a clear working definition of the concept. Potential biomarkers to measure vitality capacity were identified, and the following consensual working definition was developed: vitality capacity is a physiological state (due to normal or accelerated biological ageing processes) resulting from the interaction between multiple physiological systems, reflected in (the level of) energy and metabolism, neuromuscular function, and immune and stress response functions of the body.

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2–100) and used normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision-making.

PURPOSE: Carbohydrate (CHO) mouth rinsing (MR) prior to exercise has been shown to elicit enhanced performance and energy availability in some studies. Previous literature has concentrated on examining CHO MR strategies for improving aerobic endurance performance in younger athletic adults. Knowledge of the impact of CHO MR on functional performance in older adults is scarce. The purpose of this investigation was to determine if CHO MR would improve 6-min walk test (6MWT) performance, perceived exertion, and blood glucose responses in older adults. METHOD: Thirty-three individuals (16 males, 17 females), age ≥ 70 years performed two 6MWT trials, one of which utilized a 6.4% maltodextrin CHO MR and one of which utilized a placebo MR. Participants held the MR in their mouth for 20 s prior to the 6MWT, and trials occurred in a counterbalanced fashion. Total distance walked and rating of perceived exertion (RPE) were recorded upon completion of each 6MWT. Heart rate (HR), peripheral blood oxygen saturation (SpO2), systolic and diastolic blood pressures (BP), blood glucose, and blood lactate were measured before and after each 6MWT. RESULT: CHO MR did not alter the response of any study parameter compared to the placebo MR (p = 0.13-0.94). HR, systolic BP, and blood lactate increased and SpO2 decreased across time (p

Le muscle strie du corps humain se compose d'un continuum fonctionnel et metabolique de plusieurs types de cellules musculaires, aussi appelees fibres. On les distingue en deux grandes categories, 1. les fibres lentes (type I) et 2. les fibres rapides (types lia et llx). Ces cellules sont egalement classifiees selon le type de chaine lourde de myosine qu'elles expriment. La myosine est la principale proteine generatrice de force pour la contraction musculaire. Les fibres a contraction lente (type I) sont resistantes a la fatigue et ont un metabolisme aerobie (oxydatif). Les fibres a contraction rapide (types lia et llx) sont plus vite fatigables et ont un metabolisme anaerobie (glycolytique). Les fibres de type lia presentent toutefois des caracteristiques intermediaires de fibres rapides avec une meilleure resistance a la fatigue. Dans cette continuite il existe egalement des fibres dites hybrides, exprimant plusieurs types de chaines lourdes de myosine. Sur la base d'etudes precedentes, la proportion des fibres hybrides semble augmentee en cas d'inactivite physique et de vieillissement, mais la cinetique de leur evolution est encore meconnue. Decrites tantot comme des fibres dans un etat de transition, et tantot comme des entites a part entiere, leur role est encore debattu. Ce travail a explore le devenir des fibres hybrides en reponse a un entrainement de type endurance dans une population sedentaire et vieillissante. Vingt-deux volontaires de plus de 60 ans, sedentaires et en bonne sante, ont participe a un entrainement aerobie supervise 3 fois par semaine, d'intensite moderee, pendant une duree de 16 semaines. Dix-huit participants entraines en endurance ont servi de groupe controle. Des biopsies du muscle vastus lateralis avant et apres cette periode d'entrainement ont permis de determiner le type de 13'840 fibres par le biais d'une analyse immuno- histochimique. Avant la periode d'entrainement, un profil cellulaire a predominance de type II (lIa et llx) a ete observe dans le groupe sedentaire en comparaison au groupe control. Ceci correspond a ce qui a prealablement ete decrit dans la litterature ou une population entrainee en endurance presente une proportion plus importante de fibres lentes, et vice versa. Les fibres hybrides (l-lla et lla-llx) representaient presque 5% de toutes les fibres musculaires. Toutefois, aucune difference entre le groupe en etat « sedentaire chronique » et le groupe en etat « entraine chronique » n'a ete observee en terme de proportion de celles-ci. La periode d'entrainement a eu comme consequence de declencher une dynamique de changement de proportions de fibres musculaires vers une augmentation des fibres de type I et une diminution des fibres de type II. Ce phenomene etait accompagne par une augmentation des cellules hybrides, statistiquement significative pour les fibres de type l-lla, suggerant une contribution des fibres hybrides a une transition de fibres rapides vers des fibres lentes. Comme si les fibres hybrides servaient d'intermediaires entre les autres types de fibres musculaires. En ce qui concerne le muscle et son entrainement, cette observation serait compatible avec la notion de fibres en transition d'un type a un autre, ce qui est crucial pour la comprehension de mecanismes reversibles dans la perte de masse musculaire liee a l'âge, ainsi que le developpement de mesures preventives et therapeutiques. -- Background Human skeletal muscle is composed of a functional and metabolic continuum of slow (Type I) and fast fibers (lia and llx). Hybrid fibers co-expressing different myosin heavy chains are also present and seem to be more prominent in aging muscle. Their role is debated; hybrid fibers were reported either in a transitional state, between slow and fast fibers, or as fixed individual entities. This study examined the fate of hybrid fibers with an endurance exercise intervention in an elderly sedentary population. Methods Twenty-two sedentary healthy elderly men and women underwent a 16-week supervised endurance exercise intervention. Eighteen endurance-trained âge- and gender matched volunteers served as controls. Fiber type distribution was determined by immunohistochemistry on vastus lateralis muscle biopsies pre-intervention and post intervention. Results A total of 13840 fibers were analyzed. At baseline, a Type II dominant fiber profile was observed compared with the control group, with more Type lia (P = 0.0301) and Type llx fibers (P = 0.0328). Hybrid fibers represented almost 5% of total muscle fibers in both groups. There was no significant difference between groups (l-lla, P = 0.6719 and lia llx, P = 0.0998). Intervention triggered qualitative dynamics towards an increase in Type I, and decrease in Type II fibers, paralleled by an increase in l-lla hybrids (P = 0.0301). Conclusions The present study is, to our knowledge, the first to examine hybrid muscle fiber type adaptations to an endurance exercise intervention in the elderly. Hybrid fiber proportions did not differ between chronic sedentary state and chronic endurance-trained state. Exercise intervention increased Type l-lla hybrid fibers along with shift dynamics in other fiber types suggesting the contribution of hybrid fiber to a fast-to-slow fiber type transition, eventually serving as intermediate reservoir from one monomorphic myosin heavy chain expressing fiber type to another. This finding favours the transitional theory regarding hybrid muscle fibers and exercise, crucial to understanding reversible mechanisms of sarcopenia and development of prevention measures.

Aging and circadian rhythms are two biological processes that affect an organism, although at different time scales. Nevertheless, due to the overlap of their actions, it was speculated that both interfere or interact with each other. However, to address this question, a much deeper insight into these processes is necessary, especially at the cellular level. New methods such as single-cell RNA-sequencing (scRNA-Seq) have the potential to close this gap in our knowledge. In this review, we analyze applications of scRNA-Seq from the aging and circadian rhythm fields and highlight new findings emerging from the analysis of single cells, especially in humans or rodents. Furthermore, we judge the potential of scRNA-Seq to identify common traits of both processes. Overall, this method offers several advantages over more traditional methods analyzing gene expression and will become an important tool to unravel the link between these biological processes.

AIM: To study the association between diabetes and the prevalence of and risk factors for polypharmacy among adults aged 50 and older in England.METHODS: A cross-sectional study (2012-2013) of the English Longitudinal Study of Ageing. Polypharmacy was defined as taking 5-9 long-term medications a day and heightened polypharmacy as 10 or more. Diabetes included diagnosed and undiagnosed cases (glycated haemoglobin ≥ 6.5% (48 mmol/mol)).RESULTS: Of 7729 participants, 1100 people had diabetes and showed higher prevalence rates of polypharmacy (41.1% vs 14.8%) and heightened polypharmacy (5.8% vs 1.7%) than those without diabetes, even when antihyperglycemic medications were excluded. Risk factors for polypharmacy also differed according to diabetes status. Among people with diabetes, risk factors for polypharmacy and heightened polypharmacy were having more long-term conditions (relative risk ratio (RRR) = 1.86; 3.51) and being obese (RRR = 1.68; 3.68), while females were less likely to show polypharmacy (RRR = 0.51) and heightened polypharmacy (RRR = 0.51) than males. Older age (RRR = 1.04) was only related to polypharmacy among people without diabetes.CONCLUSIONS: Adults with diabetes had higher prevalence rates of polypharmacy and heightened polypharmacy than those without diabetes, regardless of including antihyperglycemic drugs. Early detection of polypharmacy among older people with diabetes needs to focus on co-morbidities and obesity.

The aging process occurs gradually, is highly individual, with a high degree of inter and intra-individual differences. As such, within an aging population there is significant variation in regards to extent of age related disease and functional impairment. This variability between individuals is thought to be expressed as biological age. Currently, the comprehensive geriatric assessment (CGA), a multidimensional, interdisciplinary diagnostic process is used to determine an individual's medical, psychological and functional capability at older age. However, while the CGA utilises well-established markers of physical and functional parameters, it does not include any molecular measures that indicate an individual's biological age. Combining functional measures with molecular markers of biological age, could improve the current CGA by identifying individuals undergoing a rapid aging process. In this review, the current knowledge and clinical utility of potential biomarkers of aging are presented. Although no biomarkers indicative of biological age are currently being utilized in the clinical setting promising research advancements would suggest their application in the near future.

Neurofeedback training involves presenting an individual with a representation of their brain activity and instructing them to alter the activity using the feedback. One potential application of neurofeedback is for patients to alter neural activity to improve function. For example, there is evidence that greater laterality of movement-related activity is associated with better motor outcomes after stroke; so using neurofeedback to increase laterality may provide a novel route for improving outcomes. However, we must demonstrate that individuals can control relevant neurofeedback signals. Here, we performed two proof-of-concept studies, one in younger (median age: 26years) and one in older healthy volunteers (median age: 67.5years). The purpose was to determine if participants could manipulate laterality of activity between the motor cortices using real-time fMRI neurofeedback while performing simple hand movements. The younger cohort trained using their left and right hand, the older group trained using their left hand only. In both studies participants in a neurofeedback group were able to achieve more lateralized activity than those in a sham group (younger adults: F(1,23)=4.37, p

Age has a detrimental effect on reproduction and as an increasing number of women postpone motherhood, it is imperative to assess biological age in terms of fertility prognosis and optimizing fertility treatment individually. Horvath’s epigenetic clock is a mathematical algorithm that calculates the biological age of human cells, tissues or organs based on DNA methylation levels. The clock, however, was previously shown to be highly inaccurate for the human endometrium, most likely because of the hormonal responsive nature of this tissue. The aim of this study was to determine if epigenetically based biological age of the human endometrium correlated with chronological age, when strictly timed to the same time point in the menstrual cycle. Endometrial biopsies from nine women were obtained in two consecutive cycles, both strictly timed to the LH surge (LH + 7) and additionally, peripheral whole blood samples were analyzed. Using the Illumina HumanMethylation 450 K array and Horvath’s epigenetic clock, we found a significant correlation between the biological age of the endometrium and the chronological age of the participants, although the endometrial biological age was accelerated by comparison with blood and chronological age. Moreover, similar biological ages were found in pairs of consecutive biopsies, indicating that an endometrial biopsy does not alter the biological age in the following cycle. In conclusion, as long as endometrial samples are timed to the same time point in the menstrual cycle, Horvath’s epigenetic clock could be a powerful new biomarker of reproductive aging in the human endometrium.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro‐oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin‐like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin‐like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.

ObjectiveDisadvantaged socioeconomic circumstances in early life have the potential to impact lung function. Thus, this study aimed to summarise evidence on the association between socioeconomic circumstances and respiratory function from childhood to young adulthood.DesignSystematic review and meta-analysis.MethodsFollowing the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines, Medline, ISI-Web of Science and Scopus were searched from inception up to January 2018. Original studies on the association between socioeconomic circumstances and respiratory function in early ages (ie, participants younger than 25 years of age) were investigated. Two investigators independently evaluated articles, applied the exclusion criteria, extracted data and assessed the risk of bias using the Newcastle–Ottawa Scale. A meta-analysis of the standardised mean difference and 95% CI in respiratory function between participants from different socioeconomic circumstances was conducted, using a random-effects model.ResultsThirty-three papers were included in this review and 23 showed that disadvantaged socioeconomic circumstances were significantly associated with reduced respiratory function. The meta-analysis including seven papers showed a significant difference of −0.31 (95% CI −0.42 to −0.21) litres in forced expiratory volume in the first second between children, adolescents and young adults from disadvantaged versus advantaged socioeconomic circumstances. Specifically a difference of −0.31 (95% CI −0.51 to −0.10) litres in girls and −0.43 (95% CI −0.51 to −0.35) litres in boys was observed.ConclusionsChildren, adolescents and young adults from disadvantaged socioeconomic circumstances had lower respiratory function, and boys presented higher respiratory health inequalities. This information contributes to explain the social patterning of respiratory diseases, and might enable health policy makers to tackle respiratory health inequalities at early ages.

Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti‐stress responses; these adaptations were fundamental forces during evolution. Central to anti‐stress responses are a number of short‐lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2‐related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in developmental lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics, the appearance of Diabetes Type 1 hallmarks and aging acceleration. Genetic or dietary suppression of Insulin/IGF‐like signaling (IIS) titrated Nrf2 activity to lower levels, largely normalized metabolic pathways signaling, and extended flies’ lifespan. Thus, prolonged stress signaling by otherwise cytoprotective short‐lived stress sensors perturbs IIS resulting in re‐allocation of resources from growth and longevity to somatic preservation and stress tolerance. These findings provide a reasonable explanation of why most (if not all) cytoprotective stress sensors are short‐lived proteins, and it also explains the build‐in negative feedback loops (shown here for Nrf2); the low basal levels of these proteins, and why their suppressors were favored by evolution.

Background: Accurate assessment of isometric hand grip strength (HGS) and isometric lower limb strength (LS) are often limited to specialized clinics due to high costs and need for specialized equipment and personnel. A mobile and user-friendly device would facilitate a wider use of these measures in the clinical setting. The Nintendo Wii Balance Board (WBB) is a novel and pragmatic tool that has been validated for measuring muscle strength and other clinically relevant physiological variables. However, reference data for HGS and LS are lacking. The purpose of the current study is to establish reference data for HGS and LS in individuals ≥20 years of age using the WBB method, and to characterize the effects of age in these measurements. Method: Healthy participants were recruited at various locations and their HGS and LS were tested by six assessors using the WBB. Reference data were analysed and presented in age-groups, while the age-related change in HGS and LS was tested and characterized with linear regression models. Results: Three hundred and fifty-four participants between 20 and 99 years of age were tested. Data are presented separately according to gender and the following age categories: 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80+, and presented in absolute values as well as percentiles. The main findings were; (1) Significantly higher HGS and LS among males compared to females and for the dominant limb compared to the non-dominant limb, (2) a significant decline in strength with increasing age, and (3) the rate of decline increased significantly (i.e. it was non-linear) with age for HGS, but not for LS. Conclusion: This study reported reference data with percentiles for a novel method for assessing HGS and LS. Data were consistent with previously known effects of age and gender on HGS and LS. The presented data may supplement future trials using the WBB in research or in the clinical setting.

The combination of modern interventional and preventive medicine has led to an epidemic of ageing. While this phenomenon is a positive consequence of an improved lifestyle and achievements in a society, the longer life expectancy is often accompanied by decline in quality of life due to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem. © 2017 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation.

Inhibitory control deficits represent a key aspect of the cognitive declines associated with aging. Practicing inhibitory control has thus been advanced as a potential approach to compensate for age-induced neurocognitive impairments. Yet, the functional brain changes associated with practicing inhibitory control tasks in older adults and whether they differ from those observed in young populations remains unresolved.We compared electrical neuroimaging analyses of ERPs recorded during a Go/NoGo practice session with a Group (Young; Older adults) by Session (Beginning; End of the practice) design to identify whether the practice of an inhibition task in older adults reinforces already implemented compensatory activity or reduce it by enhancing the functioning of the brain networks primarily involved in the tasks.We observed an equivalent small effect of practice on performance in the two age-groups. The topographic ERP analyses and source estimations revealed qualitatively different effects of the practice over the N2 and P3 ERP components, respectively driven by a decrease in supplementary motor area activity and an increase in left ventrolateral prefrontal activity in the older but not in the young adults with practice.Our results thus indicate that inhibition task practice in older adults increases age-related divergences in the underlying functional processes.

IntroductionHodgkin’s lymphoma (HL) has become the prototype of a curable disease. However, many young survivors suffer from late adverse effects of treatment. Both chemotherapy (CT) and radiotherapy (RT) may induce primary ovarian insufficiency (POI), which has been associated with reduced bone mineral density (BMD), neurocognitive dysfunction and possibly cardiovascular disease (CVD). While the general assumption is that POI increases CVD risk, other hypotheses postulate reverse causality, suggesting that cardiovascular risk factors determine menopausal age or that biological ageing underlies both POI and CVD risk. None of these hypotheses are supported by convincing evidence. Furthermore, most studies on POI-associated conditions have been conducted in women with early natural or surgery-induced menopause with short follow-up times. In this study, we will examine the long-term effects of CT-induced and/or RT-induced POI on BMD, cardiovascular status, neurocognitive function and quality of life in female HL survivors.Methods and analysisThis study will be performed within an existing Dutch cohort of HL survivors. Eligible women were treated for HL at ages 15–39 years in three large hospitals since 1965 and survived for ≥8 years after their diagnosis. Women visiting a survivorship care outpatient clinic will be invited for a neurocognitive, cardiovascular and BMD assessment, and asked to complete several questionnaires and to provide a blood sample. Using multivariable regression analyses, we will compare the outcomes of HL survivors who developed POI with those who did not. Cardiovascular status will also be compared with women with natural POI.Ethics and disseminationThis study has been approved by the Institutional Review Board of the Netherlands Cancer Institute and has been registered at ‘Toetsingonline’ from the Dutch Central Committee on Research involving Human Subjects (file no. NL44714.031.13). Results will be disseminated through peer-reviewed publications and will be incorporated in follow-up guidelines for HL survivors.

The aging process occurs gradually, is highly individual, with a high degree of inter and intra-individual differences. As such, within an aging population there is significant variation in regards to extent of age related disease and functional impairment. This variability between individuals is thought to be expressed as biological age. Currently, the comprehensive geriatric assessment (CGA), a multidimensional, interdisciplinary diagnostic process is used to determine an individual's medical, psychological and functional capability at older age. However, while the CGA utilises well-established markers of physical and functional parameters, it does not include any molecular measures that indicate an individual's biological age. Combining functional measures with molecular markers of biological age, could improve the current CGA by identifying individuals undergoing a rapid aging process. In this review, the current knowledge and clinical utility of potential biomarkers of aging are presented. Although no biomarkers indicative of biological age are currently being utilized in the clinical setting promising research advancements would suggest their application in the near future.

Objective : To elaborate normative values for a clinical psychophysical taste test ("Taste Strips”). Background : The "Taste Strips” are a psychophysical chemical taste test. So far, no definitive normative data had been published and only a fairly small sample size has been investigated. In light of this shortcoming for this easy, reliable and quick taste testing device, we attempted to provide normative values suitable for the clinical use. Setting : Normative value acquisition study, multicenter study. Methods : The investigation involved 537 participants reporting a normal sense of smell and taste (318 female, 219 male, mean age 44 years, age range 18-87 years). The taste test was based on spoonshaped filter paper strips ("Taste Strips”) impregnated with the four (sweet, sour, salty, and bitter) taste qualities in four different concentrations. The strips were placed on the left or right side of the anterior third of the extended tongue, resulting in a total of 32 trials. With their tongue still extended, patients had to identify the taste from a list of four descriptors, i. e., sweet, sour, salty, and bitter (multiple forcedchoice). To obtain an impression of overall gustatory function, the number of correctly identified tastes was summed up for a "taste score”. Results : Taste function decreased significantly with age. Women exhibited significantly higher taste scores than men which was true for all age groups. The taste score at the 10th percentile was selected as a cut-off value to distinguish normogeusia from hypogeusia. Results from a small series of patients with ageusia confirmed the clinical usefulness of the proposed normative values. Conclusion : The present data provide normative values for the "Taste Strips” based on over 500 subjects tested

While short-term disuse negatively affects mechanical muscle function (e.g. isometric muscle strength) little is known of the relative contribution of adaptions in central neural drive and peripheral muscle contractility. The present study investigated the relative contribution of adaptations in central neural drive and peripheral muscle contractility on changes in isometric muscle strength following short-term unilateral disuse (4 days, knee brace) and subsequent active recovery (7 days, one session of resistance training) in young (n = 11, 24 yrs) and old healthy men (n = 11, 67 yrs). Maximal isometric knee extensor strength (MVC) (isokinetic dynamometer), voluntary muscle activation (superimposed twitch technique), and electrically evoked muscle twitch force (single and doublet twitch stimulation) were assessed prior to and after disuse, and after recovery. Following disuse, relative decreases in MVC did not differ statistically between old (16.4 ± 3.7%, p < 0.05) and young (−9.7 ± 2.9%, p < 0.05) (mean ± SE), whereas voluntary muscle activation decreased more (p < 0.05) in old (−8.4 ± 3.5%, p < 0.05) compared to young (−1.1 ± 1.0%, ns) as did peak single (−25.8 ± 6.6%, p < 0.05 vs −7.6 ± 3.3%, p < 0.05) and doublet twitch force (−23.2 ± 5.5%, p < 0.05 vs −2.0 ± 2.6%, ns). All parameters were restored in young following 7 days recovery, whereas MVC and peak twitch force remained suppressed in old. Regression analysis revealed that disuse-induced changes in MVC relied more on changes in single twitch force in young (p < 0.05) and more on changes in voluntary muscle activation in old (p < 0.05), whereas recovery-induced changes in MVC mainly were explained by gains in voluntary muscle activation in both young and old. Altogether, the present data demonstrate that plasticity in voluntary muscle activation (~central neural drive) is a dominant mechanism affecting short-term disuse- and recovery-induced changes in muscle strength in older adults.

Neurofeedback training involves presenting an individual with a representation of their brain activity and instructing them to alter the activity using the feedback. One potential application of neurofeedback is for patients to alter neural activity to improve function. For example, there is evidence that greater laterality of movement-related activity is associated with better motor outcomes after stroke; so using neurofeedback to increase laterality may provide a novel route for improving outcomes. However, we must demonstrate that individuals can control relevant neurofeedback signals. Here, we performed two proof-of-concept studies, one in younger (median age: 26 years) and one in older healthy volunteers (median age: 67.5 years). The purpose was to determine if participants could manipulate laterality of activity between the motor cortices using real-time fMRI neurofeedback while performing simple hand movements. The younger cohort trained using their left and right hand, the older group trained using their left hand only. In both studies participants in a neurofeedback group were able to achieve more lateralized activity than those in a sham group (younger adults: F(1,23) = 4.37, p < 0.05; older adults: F(1,15) = 9.08, p < 0.01). Moreover, the younger cohort was able to maintain the lateralized activity for right hand movements once neurofeedback was removed. The older cohort did not maintain lateralized activity upon feedback removal, with the limitation being that they did not train with their right hand. The results provide evidence that neurofeedback can be used with executed movements to promote lateralized brain activity and thus is amenable for testing as a therapeutic intervention for patients following stroke.

Background: Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions. Objective: The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60–70 years. Methods: We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60–70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0–1). Participants were included if they reported data on ≥ 2 measurements of functional ability during a 9-year follow-up. Functional ability was scored with 6 self-reported items on activities of daily living. We performed latent class growth analysis to identify trajectories of functional decline and applied multinomial regression models to develop prediction models of identified trajectories. Analyses were stratified for sex. Results: Three distinct trajectories were identified: no/little decline (219 males, 241 females), intermediate decline (114 males, 158 females), and severe decline (36 males, 30 females). Higher gait speed showed decreased risk of functional limitations in males (intermediate limitations, odds ratio [OR] 0.74, 95% CI 0.57–0.97; severe limitations, OR 0.42, 95% CI 0.26–0.66). The final model in males further included the predictors fear of falling and alcohol intake (no/little decline, area under the receiver operating curve [AUC] 0.68, 95% CI 0.62–0.73; intermediate decline, AUC 0.63, 95% CI 0.56–0.69; severe decline, AUC 0.79, 95% CI 0.71–0.87). In females, higher gait speed showed a decreased risk of intermediate limitations (OR 0.51, 95% CI 0.38–0.68) and severe limitations (OR 0.18, 95% CI 0.07–0.44). Other predictors in females were age, living alone, economic satisfaction, balance, physical activity, BMI, and cardiovascular disease (no/little decline, AUC 0.80, 95% CI 0.75–0.85; intermediate decline, AUC 0.74, 95% CI 0.69–0.79; severe decline, AUC 0.95, 95% CI 0.91–0.99). Conclusion: Already in people aged 60–70 years, 3 distinct trajectories of functional decline were identified in these cohorts over a 9-year follow-up. Predictors of trajectories differed between males and females, except for gait speed. Identification of people at risk is the basis for targeting interventions. © 2017 The Author(s) Published by S. Karger AG, Basel. Th is article is licensed under the Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International License (CC BYNC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modifi ed material requires written permission.

The cerebellum appears to undergo late maturation in children and early decline at older age. Whether these age-related changes affect bimanual coordination performance remains unclear at best. Here, we identified the ages at which bimanual coordination performance stops improving and starts declining. In an independent cohort, we defined brain regions of interest involved in bimanual coordination using functional magnetic resonance imaging. We used these regions of interest to investigate the extent to which the gray matter of cerebellar and other brain regions explains bimanual coordination performance from 10- to 80-year-olds. Results showed that bimanual coordination performance starts declining from the age of 40 years. In participants aged 10-20 years, cerebellar lobule VI was the only significant brain predictor of bimanual coordination performance. In participants aged 60-80 years, this cerebellar region, together with the primary sensorimotor cortex, formed a group of strongest predictors. These results from 2 independent samples (10-20 and 60-80 years) suggest that cerebellar lobule VI is critical for the development and preservation of bimanual coordination skills in children and older adults, respectively. In addition, post hoc analyses suggested that the primary motor cortex mediated the adverse effect of age on bimanual coordination performance in older adults. ispartof: NEUROBIOLOGY OF AGING vol:65 pages:109-120 ispartof: location:United States status: published

Objective To assess the association of low socioeconomic status and risk factors for non-communicable diseases (diabetes, high alcohol intake, high blood pressure, obesity, physical inactivity, smoking) with loss of physical functioning at older ages. Design Multi-cohort population based study. Setting 37 cohort studies from 24 countries in Europe, the United States, Latin America, Africa, and Asia, 1990-2017 Participants 109 107 men and women aged 45-90 years. Main outcome measure Physical functioning assessed using the walking speed test, a valid index of overall functional capacity. Years of functioning lost was computed as a metric to quantify the difference in walking speed between those exposed and unexposed to low socioeconomic status and risk factors. Results According to mixed model estimations, men aged 60 and of low socioeconomic status had the same walking speed as men aged 66.6 of high socioeconomic status (years of functioning lost 6.6 years, 95% confidence interval 5.0 to 9.4). The years of functioning lost for women were 4.6 (3.6 to 6.2). In men and women, respectively, 5.7 (4.4 to 8.1) and 5.4 (4.3 to 7.3) years of functioning were lost by age 60 due to insufficient physical activity, 5.1 (3.9 to 7.0) and 7.5 (6.1 to 9.5) due to obesity, 2.3 (1.6 to 3.4) and 3.0 (2.3 to 4.0) due to hypertension, 5.6 (4.2 to 8.0) and 6.3 (4.9 to 8.4) due to diabetes, and 3.0 (2.2 to 4.3) and 0.7 (0.1 to 1.5) due to tobacco use. In analyses restricted to high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was 8.0 (5.7 to 13.1) for men and 5.4 (4.0 to 8.0) for women, whereas in low and middle income countries it was 2.6 (0.2 to 6.8) for men and 2.7 (1.0 to 5.5) for women. Within high income countries, the number of years of functioning lost attributable to low socioeconomic status by age 60 was greater in the United States than in Europe. Physical functioning continued to decline as a function of unfavourable risk factors between ages 60 and 85. Years of functioning lost were greater than years of life lost due to low socioeconomic status and non-communicable disease risk factors. Conclusions The independent association between socioeconomic status and physical functioning in old age is comparable in strength and consistency with those for established non-communicable disease risk factors. The results of this study suggest that tackling all these risk factors might substantially increase life years spent in good physical functioning. This study was supported by the European Commission (Horizon 2020 grant No 633666) and the Swiss State Secretariat for Education, Research and Innovation SERI. SS was supported by an Ambizione grant (PZ00P3_167732) from the Swiss National Science Foundation. Silvia Fraga is supported by the Portuguese Foundation for Science and Technology (SFRH/BPD/97015/2013). Various sources have supported recruitment, follow-up, and measurements in the 48 cohort studies contributing to this collaborative analysis. MK is supported by the UK Medical Research Council (K013351), NordForsk, the Nordic Programme on Health and Welfare, the Academy of Finland (311492), and the Finnish Work Environment Fund. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of this manuscript.

Studies examining how diet affects mortality risk over age typically characterise mortality using parameters such as aging rates, which condense how much and how quickly the risk of dying changes over time into a single measure. Demographers have suggested that decoupling the tempo and the magnitude of changing mortality risk may facilitate comparative analyses of mortality trajectories, but it is unclear what biologically meaningful information this approach offers. Here, we determine how the amount and ratio of protein and carbohydrate ingested by female Drosophila melanogaster affects how much mortality risk increases over a time-standardised life-course (the shape of aging) and the tempo at which animals live and die (the pace of aging). We find that pace values increased as flies consumed more carbohydrate but declined with increasing protein consumption. Shape values were independent of protein intake but were lowest in flies consuming ~90 μg of carbohydrate daily. As protein intake only affected the pace of aging, varying protein intake rescaled mortality trajectories (i.e. stretched or compressed survival curves), while varying carbohydrate consumption caused deviation from temporal rescaling (i.e. changed the topography of time-standardised survival curves), by affecting pace and shape. Clearly, the pace and shape of aging may vary independently in response to dietary manipulation. This suggests that there is the potential for pace and shape to evolve independently of one another and respond to different physiological processes. Understanding the mechanisms responsible for independent variation in pace and shape, may offer insight into the factors underlying diverse mortality trajectories. Electronic supplementary material The online version of this article (doi:10.1007/s10522-017-9729-1) contains supplementary material, which is available to authorized users.

BACKGROUND: Muscle mass, strength, and power are known determinants of mobility in older adults but there is limited knowledge on the influence of muscle architecture or tendon properties on mobility. The purpose of this study was to examine the relationship between mobility and plantarflexor muscle-tendon properties in healthy older adults.METHODS: A total of 52 subjects (age 70-81 years) were measured for 6-minute walk test (6MWT), timed "up and go"-test (TUG), isometric plantarflexion strength, Achilles tendon stiffness, triceps surae muscle architecture, lower extremity lean mass, isometric leg extension strength, and leg extension power. Partial correlations and multivariate regression models adjusted for sex, age, body mass, and height were used to examine the relationship between mobility (6MWT and TUG) and lower limb muscle-tendon properties.RESULTS: Multivariate regression models revealed that Achilles tendon stiffness (p = .020), plantarflexion strength (p = .022), and medial gastrocnemius fascicle length (p = .046) were independently associated with 6MWT. Plantarflexion strength (p = .037) and soleus fascicle length (p = .031) were independently associated with TUG.CONCLUSIONS: Plantarflexor muscle-tendon properties were associated with mobility in older adults independent of lower extremity lean mass, leg extension strength, or power. Plantarflexion strength was a stronger predictor of mobility than leg extension strength or power. The novel finding of this study was that muscle architecture and tendon properties explained interindividual differences in mobility. This study highlights the importance of the plantarflexors for mobility in older adults and provides understanding of possible mechanisms of age-related decline in mobility.

Multisensory information typically confers neural and behavioural advantages over unisensory information. We used a simple audio-visual detection task to compare healthy young (HY), healthy older (HO) and mild-cognitive impairment (MCI) individuals. Neuropsychological tests assessed individuals' learning and memory impairments. First, we provide much-needed clarification regarding the presence of enhanced multisensory benefits in both healthily and abnormally aging individuals. The pattern of sensory dominance shifted with healthy and abnormal aging to favour a propensity of auditory-dominant behaviour (i.e., detecting sounds faster than flashes). Notably, multisensory benefits were larger only in healthy older than younger individuals who were also visually-dominant. Second, we demonstrate that the multisensory detection task offers benefits as a time- and resource-economic MCI screening tool. Receiver operating characteristic (ROC) analysis demonstrated that MCI diagnosis could be reliably achieved based on the combination of indices of multisensory integration together with indices of sensory dominance. Our findings showcase the importance of sensory profiles in determining multisensory benefits in healthy and abnormal aging. Crucially, our findings open an exciting possibility for multisensory detection tasks to be used as a cost-effective screening tool. These findings clarify relationships between multisensory and memory functions in aging, while offering new avenues for improved dementia diagnostics.

Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or aging, we have used acute diphtheria toxin−mediated cell ablation to reduce Sertoli cell population size. Results show that the size of the Sertoli cell population that forms during development determines the number of germ cells and Leydig cells that will be present in the adult testis. Similarly, the number of germ cells and Leydig cells that can be maintained in the adult depends directly on the size of the adult Sertoli cell population. Finally, we have used linear modeling to generate predictive models of testis cell composition during development and in the adult based on the size of the Sertoli cell population. This study shows that at all ages the size of the Sertoli cell population is predictive of resulting testicular cell composition. A reduction in Sertoli cell number/proliferation at any age will therefore lead to a proportional decrease in germ cell and Leydig cell numbers, with likely consequential effects on fertility and health., Sertoli cell knockout studies show that the numbers of Leydig cells and germ cells that develop and are maintained in the testis are directly proportional to the number of Sertoli cells.

Objectives This study aims to identify and explain the continuum in which older people in Singapore participate in community and social life, highlighting the influence of culture and policy context on social participation. Methods Using an ethnographic approach in a neighbourhood (n = 109), we conducted focus groups with older adults of different ethnicities, exploring experiences of social participation. Next, participants took 50 photographs relating to ‘lives of elders’, showcasing the socio-ecological context that influenced social participation. Lastly, go-along interviews were conducted in various precincts with community leaders. Results A continuum of social participation emerged among older adults, ranging from (1) marginalization and exclusion, to (2) ‘comfort-zoning’ alone (3) seeking consistent social interactions, (4) expansion of social network, and (5) giving back to society. Seeking consistent social interactions was shaped by a preference for cultural grouping and ethnic values, but also a desire for emotional safety. Attitudes about expanding one's social network depended on the psychosocial adjustment of the older person to the prospect of gossip and ‘trouble’ of managing social relations. Despite the societal desirability of an active ageing lifestyle, cultural scripts emphasizing family meant older adults organized participation in social and community life, around family responsibilities. Institutionalizing family reliance in Singapore's welfare approach penalized lower-income older adults with little family support from accessing subsidies, and left some living on the margins. Discussion To promote inclusiveness, ageing programs should address preferences for social participation, overcoming barriers at the individual, ethnic culture and policy level.

In adult neurogenesis young neurons connect to the existing network via formation of thousands of new synapses. At early developmental stages, glutamatergic synapses are sparse, immature and functionally 'silent', expressing mainly NMDA receptors. Here we show in 2- to 3-week-old young neurons of adult mice, that brief-burst activity in glutamatergic fibers is sufficient to induce postsynaptic AP firing in the absence of AMPA receptors. The enhanced excitability of the young neurons lead to efficient temporal summation of small NMDA currents, dynamic unblocking of silent synapses and NMDA-receptor-dependent AP firing. Therefore, early synaptic inputs are powerfully converted into reliable spiking output. Furthermore, due to high synaptic gain, small dendritic trees and sparse connectivity, neighboring young neurons are activated by different distinct subsets of afferent fibers with minimal overlap. Taken together, synaptic recruitment of young neurons generates sparse and orthogonal AP firing, which may support sparse coding during hippocampal information processing.

Background: Living independently can be challenging for seniors. Technologies are expected to help older adults age in place, yet little empirical research is available on how seniors develop a need for technologies, how they acquire these technologies, and how these subsequently affect their lives. Aging is complex, dynamic and personal. But how does this translate to seniors’ adoption and acceptance of technology? To better understand origins and consequences of technology acquirement by independent-living seniors, an explorative longitudinal qualitative field study was set up.Methods: Home visits were made to 33 community-dwelling seniors living in the Netherlands, on three occasions (2012–2014). Semi-structured interviews were conducted on the timeline of acquirements, and people and factors involved in acquirements. Additionally, participants were interviewed on experiences in using technologies since acquirement. Thematic analysis was employed to analyze interview transcripts, using a realist approach to better understand the contexts, mechanisms and outcomes of technology acquirements.Results: Findings were accumulated in a new conceptual model: The Cycle of Technology Acquirement by Independent-Living Seniors (C-TAILS), which provides an integrative perspective on why and how technologies are acquired, and why these may or may not prove to be appropriate and effective, considering an independent-living senior’s needs and circumstances at a given point in time. We found that externally driven and purely desire-driven acquirements led to a higher risk of suboptimal use and low levels of need satisfaction.Conclusions: Technology acquirement by independent-living seniors may be best characterized as a heterogeneous process with many different origins, pathways and consequences. Furthermore, technologies that are acquired in waysthat are not congruent with seniors’ personal needs and circumstances run a higher risk of proving to be ineffective or inappropriate. Yet, these needs and circumstances are subject to change, and the C-TAILS model can be employed tobetter understand contexts and mechanisms that come into play.

Objectives In this study, the authors sought to obtain hemodynamic estimates across a wide age span and in both sexes for future reference and compare these estimates with current guideline diagnostic hemodynamic thresholds for abnormal filling pressure and pulmonary hypertension. Background At present, the influence of age on hemodynamic function is largely unknown. Because many diseases with proposed cardiac impact are more prevalent in the older population, it is pivotal to know how hemodynamic parameters are affected by age itself to discern the influence of disease from that of physiological aging. Methods Sixty-two healthy participants, evenly distributed with respect to age (20 to 80 years) and sex (32 women/30 men), were prospectively enrolled in the study. Participants were all deemed healthy by medical history, echocardiography, exercise test, spirometry, blood tests, and electrocardiogram. Participants had hemodynamic parameters measured using right heart catheterization during rest, passive leg raise, and incremental exercise. Results During rest, all hemodynamic parameters were similar between age groups, apart from blood pressure. During leg raise and incremental exercise, there was augmented filling pressure (p < 0.0001) and diminished cardiac output (p = 0.001) and hence a higher pressure:flow ratio (pulmonary artery pressure/capillary wedge pressure to cardiac output) with progressive age, evident from the earliest ages. All indexed hemodynamic measures were similar between sexes. The diagnostic threshold (pulmonary capillary wedge pressure ≥25 mm Hg) currently used during exercise testing to diagnose abnormal left ventricular filling pressure was measured in 30% of our healthy elderly participants. Conclusions Cardiac aging was progressive without sex differences in healthy participants. The hemodynamic reference values obtained suggest that the diagnostic threshold for abnormal filling pressure should be individually determined according to age of the patient.

Background: Orthostatic hypotension (OH) is common in older adults and associated with increased morbidity and mortality, loss of independence and high health-care costs. Standing up slowly is a recommended non-pharmacological intervention. However, the effectiveness of this advice has not been well studied. Objectives: The aim of this study was to investigate whether standing up slowly antagonises posture-related blood pressure (BP) decrease in a clinically relevant population of geriatric outpatients. Methods: In this cross-sectional study, 24 community-dwelling older adults referred to a geriatric outpatient clinic and diagnosed with OH were included. BP was measured continuously during 3 consecutive transitions from supine to standing position during normal, slow and fast transition. Results: The relative BP decrease at 0-15 s after slow transition was significantly lower than after normal transition (p = 0.003 for both systolic BP and diastolic BP) and fast transition (p = 0.045 for systolic BP; diastolic BP: non-significant). The relative diastolic BP decrease at 60-180 s after normal transition was significantly lower than after fast transition (p = 0.029). Conclusion: Standing up slowly antagonises BP decrease predominantly during the first 15 s of standing up in a clinically relevant population of geriatric outpatients diagnosed with OH. Results support the non-pharmacological intervention in clinical practice to counteract OH.

CONTEXT: Sarcopenia is thought to be associated with mitochondrial (Mito) loss. It is unclear whether the decrease in Mito content is consequent to aging per se or to decreased physical activity. OBJECTIVES: The objective of the study was to examine the influence of fitness on Mito content and function and to assess whether exercise could improve Mito function in older adults. DESIGN AND SUBJECTS: Three distinct studies were conducted: 1) a cross-sectional observation comparing Mito content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults and sedentary (S) subjects matched for age and gender; and 3) a 4-month exercise intervention in S. SETTING: The study was conducted at a university-based clinical research center. OUTCOMES: Mito volume density (MitoVd) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins by Western blotting, mRNAs for transcription factors involved in M biogenesis by quantitative RT-PCR, and in vivo oxidative capacity (ATPmax) by (31)P-magnetice resonance spectroscopy. Peak oxygen uptake was measured by graded exercise test. RESULTS: Peak oxygen uptake was strongly correlated with MitoVd in 80 60- to 80-year-old adults. Comparison of chronically endurance-trained older adults vs S revealed differences in MitoVd, ATPmax, and some electron transport chain protein complexes. Finally, exercise intervention confirmed that S subjects are able to recover MitoVd, ATPmax, and specific transcription factors. CONCLUSIONS: These data suggest the following: 1) aging per se is not the primary culprit leading to Mito dysfunction; 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle Mito content and may prevent aging muscle comorbidities; and 3) the improvement of Mito function is all about content.

International audience; During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway. Our findings suggest that during ageing there is no downregulation of IGF1/Akt pathway and that sarcopenia is not due to FoxO activation and upregulation of the proteolytic systems. A potentially interesting result was the increased phosphorylation of the ribosomal protein S6, indicative of increased activation of mTOR complex1 (mTORC1), in aged mice. This result may provide the rationale why rapamycin treatment and caloric restriction promote longevity, since both interventions blunt activation of mTORC1; however, this change was not statistically significant in humans. Finally, genetic perturbation of these pathways in old mice aimed at promoting muscle hypertrophy via Akt overexpression or preventing muscle loss through inactivation of the ubiquitin ligase atrogin1 were found to paradoxically cause muscle pathology and reduce lifespan, suggesting that drastic activation of the IGF1-Akt pathway may be counterproductive, and that sarcopenia is accelerated, not delayed, when protein degradation pathways are impaired.